title: Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function.
abstract: Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure.
authors.affiliation: Division of Preventive Medicine and Nutrition and.
authors.forename: Raffay S
authors.initials: RS
authors.lastname: Khan
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.forename: Ni-Huiping
authors.initials: NH
authors.lastname: Son
authors.forename: Kalyani G
authors.initials: KG
authors.lastname: Bharadwaj
authors.forename: Carla
authors.initials: C
authors.lastname: Palacios
authors.forename: Aalap
authors.initials: A
authors.lastname: Chokshi
authors.forename: Ruiping
authors.initials: R
authors.lastname: Ji
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Yu
authors.forename: Sunichi
authors.initials: S
authors.lastname: Homma
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D004452:Echocardiography; D004734:Energy Metabolism / Q000235:genetics*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006321:Heart / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; C551613:Myh7 protein, mouse; C495678:Slc2a1 protein, mouse; D014280:Triglycerides; D000255:Adenosine Triphosphate; D008071:Lipoprotein Lipase; D018995:Myosin Heavy Chains
keywords: energetics; glucose; glucose transporters; heart failure; lactate; triglyceride